To compare the response of the medial amygdala and central amygdala to juvenile social subjugation (JSS), we used unbiased stereology to quantify the immediate early gene product Fos in prepubertal rats after aggressive or benign social encounters or handling. We estimated the overall number of neurons and the proportion of Fos immunoreactive neurons in the posterodorsal (MePD) and posteroventral medial amygdala (MePV) and the central amygdala (CeA). Experience elicited Fos in a sex- and hemisphere-dependent manner in the MePD. The left MePD was selective for JSS in both sexes, but the right MePD showed a specific Fos response to JSS in males only. In the MePV, irrespective of hemisphere or sex, JSS elicited the greatest amount of Fos, benign social experience elicited an intermediate level, and handling the least. None of the experiential conditions elicited significant levels of Fos in the CeA. We found a previously unreported sex difference in the number of CeA neurons (M>F) that was highly significant and a strong trend toward a sex difference (M>F) in the MePD. These data show that the posterior MeA subnuclei are more responsive to JSS than to benign social interaction, that sex interacts with hemispheric laterality to determine the response of the MePD to JSS and that the MePV responds to social experience and JSS. Taken together, these findings support the hypothesis that juvenile rats process JSS in a sex-specific manner. 相似文献
Dysregulation in corticotropin-releasing hormone (CRH) secretion in the hypothalamus-pituitary-adrenal (HPA) axis may be involved in the etiology of major depressive disorder (MDD). Chronic therapy with standard antidepressant drugs, such as imipramine, can downregulate HPA axis function, indicating that the HPA axis may be an important target for antidepressant action. We tested several doses of a standardized commercial preparation of Hypericum perforatum plant extract (popularly known as St. John's Wort), a medicinal herb used for treating mild depressive symptoms, to determine whether it also modulated HPA axis function. Chronic imipramine treatment (daily injections for 8 weeks) of male Sprague-Dawley rats significantly downregulated circulating plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone compared to animals treated with saline. However, chronic St. John's Wort treatment (daily gavage for 8 weeks) had no effect on plasma ACTH or corticosterone, even at the highest doses tested. Our results confirm previous findings that imipramine may have significant peripheral HPA axis-mediated effects. However, our data does not support any role for H. perforatum in modulation of HPA axis function, suggesting that alternative pathways may be involved in mediating its antidepressant effects. 相似文献
Cardiomyocyte tumour necrosis factor α (TNF‐α) production contributes to myocardial depression during sepsis. This study was designed to observe the effect of norepinephrine (NE) on lipopolysaccharide (LPS)‐induced cardiomyocyte TNF‐α expression and to further investigate the underlying mechanisms in neonatal rat cardiomyocytes and endotoxaemic mice. In cultured neonatal rat cardiomyocytes, NE inhibited LPS‐induced TNF‐α production in a dose‐dependent manner. α1‐ adrenoceptor (AR) antagonist (prazosin), but neither β1‐ nor β2‐AR antagonist, abrogated the inhibitory effect of NE on LPS‐stimulated TNF‐α production. Furthermore, phenylephrine (PE), an α1‐AR agonist, also suppressed LPS‐induced TNF‐α production. NE inhibited p38 phosphorylation and NF‐κB activation, but enhanced extracellular signal‐regulated kinase 1/2 (ERK1/2) phosphorylation and c‐Fos expression in LPS‐treated cardiomyocytes, all of which were reversed by prazosin pre‐treatment. To determine whether ERK1/2 regulates c‐Fos expression, p38 phosphorylation, NF‐κB activation and TNF‐α production, cardiomyocytes were also treated with U0126, a selective ERK1/2 inhibitor. Treatment with U0126 reversed the effects of NE on c‐Fos expression, p38 mitogen‐activated protein kinase (MAPK) phosphorylation and TNF‐α production, but not NF‐κB activation in LPS‐challenged cardiomyocytes. In addition, pre‐treatment with SB202190, a p38 MAPK inhibitor, partly inhibited LPS‐induced TNF‐α production in cardiomyocytes. In endotoxaemic mice, PE promoted myocardial ERK1/2 phosphorylation and c‐Fos expression, inhibited p38 phosphorylation and IκBα degradation, reduced myocardial TNF‐α production and prevented LPS‐provoked cardiac dysfunction. Altogether, these findings indicate that activation of α1‐AR by NE suppresses LPS‐induced cardiomyocyte TNF‐α expression and improves cardiac dysfunction during endotoxaemia via promoting myocardial ERK phosphorylation and suppressing NF‐κB activation. 相似文献
Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a fluorescence‐activated cell sorting (FACS)‐based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats. We now describe a modified FACS‐based method to characterize molecular alterations in Fos‐expressing dorsal striatal neurons from a single rat using a multiplex pre‐amplification strategy. Fos and NeuN (a neuronal marker) immunohistochemistry indicate that 5–6% of dorsal striatum neurons were activated 90 min after acute methamphetamine injections (5 mg/kg, i.p.) while less than 0.5% of neurons were activated by saline injections. We used FACS to separate NeuN‐labeled neurons into Fos‐positive and Fos‐negative neurons and assessed mRNA expression using RT‐qPCR from as little as five Fos‐positive neurons. Methamphetamine induced 3–20‐fold increases of immediate early genes arc, homer‐2, c‐fos, fosB, and its isoforms (ΔfosB and a novel isoform ΔfosB‐2) in Fos‐positive but not Fos‐negative neurons. Immediate early gene mRNA induction was 10‐fold lower or absent when assessed in unsorted samples from single dorsal striatum homogenates. Our modified method makes it feasible to study unique molecular alterations in neurons activated by drugs or drug‐associated cues in complex addiction models.
Corticosterone plays an important role in feeding behavior. However, its mechanism remains unclear. Therefore, the present study aimed to investigate the effect of corticosterone on feeding behavior. In this study, cumulative food intake was increased by acute corticosterone administration in a dose‐dependent manner. Administration of the 5‐HT2c receptor agonist m‐chlorophenylpiperazin (mCPP) reversed the effect of corticosterone on food intake. The anorectic effects of mCPP were also blocked by the 5‐HT2c receptor antagonist RS102221 in corticosterone‐treated mice. Both corticosterone and mCPP increased c‐Fos expression in hypothalamic nuclei, but not the nucleus of the solitary tract. RS102221 inhibited c‐Fos expression induced by mCPP, but not corticosterone. In addition, mCPP had little effect on TH and POMC levels in the hypothalamus. Furthermore, mCPP antagonized decreasing effect of the leptin produced by corticosterone. Taken together, our findings suggest that 5‐HT2c receptors and leptin may be involved in the effects of corticosterone‐induced hyperphagia. 相似文献
Acute fasting induced antidepressant‐like effects. However, the exact brain region and mechanism of these actions are still largely unknown. Therefore, in this study the antidepressant‐like effects of acute fasting on c‐Fos expression and BDNF levels were investigated. Consistent with our previous findings, immobility time was remarkably shortened by 9 hrs fasting in the forced swimming test. Furthermore, these antidepressant‐like effects of 9 fasting were inhibited by a 5‐HT2A/2C receptor agonist (±)‐1‐(2, 5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane hydrochloride (DOI), and the effect of DOI was blocked by pretreatment with a selective 5‐HT2A receptor antagonist ketanserin. Immunohistochemical study has shown that c‐Fos level was significantly increased by 9 hrs fasting in prefrontal cortex but not hippocampus and habenular. Fasting‐induced c‐Fos expression was further enhanced by DOI in prefrontal cortex, and these enhancements were inhibited by ketanserin. The increased BDNF levels by fasting were markedly inhibited by DOI in frontal cortex and hippocampus, and these effects of DOI on BDNF levels were also blocked by ketanserin. These findings suggest that the antidepressant‐like effects of acute fasting may be exerted via 5‐HT2A receptor and particularly sensitive to neural activity in the prefrontal cortex. Furthermore, these antidepressant‐like effects are also mediated by CREB and BDNF pathway in hippocampus and frontal cortex. Therefore, fasting may be potentially helpful against depression. 相似文献
Impaired fear memory extinction (Ext) is one of the hallmark symptoms of post‐traumatic stress disorder (PTSD). However, since the precise mechanism of impaired Ext remains unknown, effective interventions have not yet been established. Recently, hippocampal‐prefrontal brain‐derived neurotrophic factor (BDNF) activity was shown to be crucial for Ext in naïve rats. We therefore examined whether decreased hippocampal‐prefrontal BDNF activity is also involved in the Ext of rats subjected to a single prolonged stress (SPS) as a model of PTSD. BDNF levels were measured by enzyme‐linked immunosorbent assay (ELISA), and phosphorylation of TrkB was measured by immunohistochemistry in the hippocampus and medial prefrontal cortex (mPFC) of SPS rats. We also examined whether BDNF infusion into the ventral mPFC or hippocampus alleviated the impaired Ext of SPS rats in the contextual fear conditioning paradigm. SPS significantly decreased the levels of BDNF in both the hippocampus and mPFC and TrkB phosphorylation in the ventral mPFC. Infusion of BDNF 24 hours after conditioning in the infralimbic cortex (ILC), but not the prelimbic cortex (PLC) nor hippocampus, alleviated the impairment of Ext. Since amelioration of impaired Ext by BDNF infusion did not occur without extinction training, it seems the two interventions must occur consecutively to alleviate impaired Ext. Additionally, BDNF infusion markedly increased TrkB phosphorylation in the ILC of SPS rats. These findings suggest that decreased BDNF signal transduction might be involved in the impaired Ext of SPS rats, and that activation of the BDNF‐TrkB signal might be a novel therapeutic strategy for the impaired Ext by stress. 相似文献
Cue‐induced heroin seeking after prolonged withdrawal is associated with neuronal activation and altered gene expression in prefrontal cortex (PFC). However, these previous studies assessed gene expression in all neurons regardless of their activity state during heroin seeking. Using Fos as a marker of neural activity, we describe distinct molecular alterations induced in activated versus non‐activated neurons during cue‐induced heroin seeking after prolonged withdrawal. We trained rats to self‐administer heroin for 10 days (6 h/day) and assessed cue‐induced heroin seeking in extinction tests after 14 or 30 days. We used fluorescent‐activated cell sorting (FACS) to purify Fos‐positive and Fos‐negative neurons from PFC 90 min after extinction testing. Flow cytometry showed that Fos‐immunoreactivity was increased in less than 10% of sparsely distributed PFC neurons. mRNA levels of the immediate early genes fosB, arc, egr1, and egr2, as well as npy and map2k6, were increased in Fos‐positive, but not Fos‐negative, neurons. In support of these findings, double‐label immunohistochemistry indicated substantial coexpression of neuropeptide Y (NPY)‐ and Arc‐immunoreactivity in Fos‐positive neurons. Our data indicate that cue‐induced relapse to heroin seeking after prolonged withdrawal induces unique molecular alterations within activated PFC neurons that are distinct from those observed in the surrounding majority of non‐activated neurons. 相似文献
To develop an index of the activation of abdominal sympathetic nerves, we used Fos immunostaining of the celiac ganglion (CG) taken from rats receiving nicotine, preganglionic nerve stimulation, or glucopenic agents. Subcutaneous nicotine injection moderately increased Fos expression in the principal ganglionic cells of the CG (17 +/- 4 Fos+ per mm(2), approximately 12% of all principal CG cells), whereas subcutaneous saline had no effect (0 +/- 0 Fos+ per mm(2); n = 7; P < 0.01). Greater Fos expression was obtained by applying nicotine topically to the CG (71 +/- 8 Fos+ per mm(2); 52% of all principal CG cells, n = 5; P < 0.01 vs. topical saline, n = 4) and by preganglionic nerve stimulation (126 +/- 9 Fos+ per mm(2); 94% of all principal CG cells, n = 11; P < 0.01 vs. nerve isolation, n = 7). Moderate Fos expression was also observed in the CG after intraperitoneal 2-deoxy-D-glucose (2DG) injection (21 +/- 2 Fos+ per mm(2); 16% of all principal CG cells, n = 5; P < 0.01 vs. saline ip) or insulin injection (16 +/- 2 Fos+ per mm(2); 12% of all principal CG cells, n = 6; P < 0.01 vs. saline ip). Furthermore, Fos expression induced by 2DG was dose and time dependent. These data demonstrate significant Fos expression in the CG in response to chemical, electrical, and reflexive stimulation. Thus Fos expression in the CG may be a useful index to describe various levels of activation of its postganglionic sympathetic neurons. 相似文献